protocolLICAVAL : combination therapy in acute and maintenance treatment of bipolar disorder

Background: The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (efficacy and tolerability of the combination of LIthium and CArbamazepine compared to lithium and VALproic acid in the treatment of young bipolar patients) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs. Methods: LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study. Results: LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012. Conclusions: Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease. Trial registration: ClinicalTrials.gov Identifier: NCT00976794 Background Bipolar Disorder (BD) treatment is a topic in evolution as long as the understanding of the clinical features, and possible pathophysiology, still progress. Due to multivariate factors associated with its cause and the variability of clinical presentations it's hard to determine a specific treatment with best outcome (efficacy and tolerability). Some difficulties in the BD treatment include: delay in diagnosis, high levels of comorbidity, frequent treatment nonadherence and high risk of relapse/recurrence (mainly in the presence of residual symptoms) [1]. Most treatments focus on acute phase and the measure of response as a reduction in symptoms of at least 50% from baseline. In fact, a number of patients who responded to treatment continue to experience significant subsyndromic symptoms. A small number of studies reported remission rates, which mean at least 2 months with no significant signs or symptoms of the disorder [2]. Fewer studies reported remission during acute phase through maintenance phase of treatment and its predictors [3] what is of great clinical significance. Recent data showed that BD treatment in special conditions was associated with full remission in only half of the patients and that nearly half of the recovered patients relapsed at least once during the two year of follow up [4]. Maintenance treatment is necessary in BD due to its great mortality, morbidity risk and social and professional impairment associated with its poorer outcome [5]. Lithium is first line choice for the maintenance treatment of BD, mainly for classic (euphoric) mania and bipo* Correspondence: rmoreno@hcnet.usp.br 1 Department and Institute of Psychiatry, Clinical Hospital, University of Sao Paulo, School of Medicine, Brazil Full list of author information is available at the end of the article © 2010 Campos et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Campos et al. Trials 2010, 11:72 http://www.trialsjournal.com/content/11/1/72 Page 2 of 5 lar depression according to many open controlled studies, with additional clinical effects such as: antisuicidal properties; augmentation and treatment of acute unipolar depression and recurrent depression [6]. The accumulating data tend to support its specificity in psychiatric usage, specially in those patients with "classic" BD. Available clinical trial suggest that better response to valproate are related to dysphoric or mixed episodes and rapid cycling patients [7]. Recently, valproate evidenced benefits on depressive aspects of BD both on acute and prophylactic use [8]. Carbamazepine is associated with better response in: not receiving treatment with mood stabilizers previously; atypical symptoms and signs; dysphoric and rapid cycling patients; treatment resistance to lithium therapy; under 30 years; no family history of BD [7]. Carbamazepine and valproate appear to be effective in the prophylactic treatment of bipolar disorder, especially in combination with lithium, although further studies are desirable [9]. In Brazil lithium is the first treatment choice in all BD phases representing an appropriate treatment of accessible cost. Treatment in the Brazilian Public Health System (Sistema único de Saúde SUS) have financial limitations once atypical antipsychotics and some anticonvulsants are not available for use in BD. Therefore, the most used treatments for the general population present smaller number of controlled studies in relation to the newest medications in which the pharmaceutical industry has interest in spreading. Although medications such as lithium, valproic acid and carbamazepine have been used for a long time, studies comparing effectiveness and other outcome measures, as well as data of long term combination treatment can still help the adaptation of the public health politics to the patient's real needs (Taveira and Moreno: Survey on treatment of bipolar disorder in Brazil: psychiatrists' epidemiology, prescription drugs and impact on heath policies. Submitted.)